The clinical and biological effects of prenatal administration of fluorides in an effort to prevent dental caries in the offspring are incompletely defined. Although numerous studies have explored maternal-fetal fluoride metabolism and uptake of fluoride in fetal hard tissues, the data were of limited value because of difficulties in accurately assaying for the low plasma [F], especially in fetal plasma where levels are extremely low. Also, a practical, relevant and relatively inexpensive animal model system had not been established. We have refined the analytical method to provide accurate assay of F at the low levels involved. And, we have established the guinea pig as useful, relevant model system for controlled experiments. This project is designed to extend our studies of the parameters and mechanisms concerning the placental transfer of fluorides, using the guinea pig as the model system. The proposed work is a logical extension of our previous studies, especially the findings resulting from experiments conducted with the support of our currently funded project grant (grant period: 8/1/86-7/31/89). Certain of the basic parameters of maternal- fetal fluoride metabolism have been established. Our data provide the basis for a hypothesis concerning the mathematical relationship between maternal plasma [F], fetal plasma [F], and enamel plasma [F]. This hypothesis should be tested. The effects of prenatal fluoride exposure on F uptake in enamel postnatally need to be explored. And, the basic mechanisms in placental transfer of F and F clearance from fetal plasma can now be studied. The project includes three Specific Aims: (1) To test the hypothesis that [F] in fetal plasma and developing enamel bear definable mathematical relationships to maternal plasma [F] when variations in chronic F exposure occur during gestation. The relationship between variations in maternal dose and maternal plasma [F] also will be established. (2) To determine the effect of prenatal fluoride status on F uptake in developing enamel postnatally. (3) To explore the mechanisms involved in the placental transfer of F and clearance from the fetal plasma.